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Early Vascular Adjustments During Hypertensive Pregnancy (EVA)

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ClinicalTrials.gov Identifier: NCT02531490
Recruitment Status : Recruiting
First Posted : August 24, 2015
Last Update Posted : October 3, 2019
Sponsor:
Information provided by (Responsible Party):
Maastricht University Medical Center

Tracking Information
First Submitted Date  ICMJE August 5, 2015
First Posted Date  ICMJE August 24, 2015
Last Update Posted Date October 3, 2019
Actual Study Start Date  ICMJE January 1, 2015
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 21, 2015)
  • number of patients with severe gestational hypertension [ Time Frame: from date of randomization until the date of this study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
    Systolic blood pressure ≥ 160mmHg and/or diastolic blood pressure ≥ 110mmHg, measured at every visit
  • number of patients with preeclampsia [ Time Frame: from date of randomization until the date of this study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
    Preeclampsia is defined as the coexistence of de novo hypertension after 20 weeks of gestation and one or more of the following new-onset conditions:
    1. Proteinuria (spot urine protein/creatinine ≥ 30g/mol or ≥ 300mg/day or at least 1 g/L [2+] on dipstick testing).
    2. Other maternal organ dysfunction:
      • Renal insufficiency (creatinine levels ≥ 90μmol/L);
      • Liver involvement (elevated transaminases: ASAT ≥31 U/L and/or ALAT ≥34U/L);
      • Neurological complications (hyperreflexia when accompanied by clonus and/or severe headaches, persistent visual scotomata, altered mental status, eclampsia);
      • Haematological complications (thrombocytopenia, platelet count below 150.000/dL, disseminated intravascular coagulation, haemolysis).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 25, 2015)
  • the pattern of change of the hemodynamic profile, measured by the ratio of mean arterial pressure and heart rate. [ Time Frame: at baseline and each study visit/follow up measurement (at 1 week, 2 weeks, etc. up to 23 weeks after inclusion. The expected average is 8 weeks ]
    hemodynamic profiles will be classified as hyperdynamic, hypodynamic vasocontricted or mixed profile.
  • hemodynamic profile by mean arterial pressure/heart rate ratio [ Time Frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
    hemodynamic profiles will be classified as hyperdynamic, hypodynamic vasocontricted or mixed profile.
  • diameter aortic outflow tract and left ventricular outflow tract measured by transthoracic echocardiography [ Time Frame: from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached) ]
    cardiac output can be derived from these values + heart rate
  • left ventricular volume after diastole and systole measured by transthoracic echocardiography [ Time Frame: from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached) ]
    ejection fraction can be derived from these values
  • diameter aortic outflow tract and left ventricular outflow tract measured by transthoracic echocardiography [ Time Frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
    cardiac output can be derived from these values + heart rate
  • left ventricular volume after diastole and systole measured by transthoracic echocardiography [ Time Frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
    ejection fraction can be derived from these values
  • cardiac remodeling during pregnancy: number of patients with concentric left ventricular remodeling or concentric hypertrophy. [ Time Frame: from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached) ]
    Echocardiographic concentric left ventricular (LV) remodelling and hypertrophy. Concentric remodeling is defined as a relative wall thickness (RWT) <=0.43 with a Left Ventricular Mass index (LVMi) of <95 gram/m2. Concentric hypertrophy is defined as a RWT <0.43 with a LVMi of ≥95 gram/m2.
  • cardiac remodeling during pregnancy: number of patients with concentric left ventricular remodeling or concentric hypertrophy. [ Time Frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
    Echocardiographic concentric left ventricular (LV) remodelling and hypertrophy. Concentric remodeling is defined as a relative wall thickness (RWT) <=0.43 with a Left Ventricular Mass index (LVMi) of <95 gram/m2. Concentric hypertrophy is defined as a RWT <0.43 with a LVMi of ≥95 gram/m2.
  • health status of the newborn by Apgar score [ Time Frame: assessed immediately after delivery ]
    scored by gynecologist or paediatrician on a scale of 1 to 10
  • prevalence of small for gestational age infancy [ Time Frame: assessed at delivery date ]
    birth weight and percentile combined with gestational age at delivery
  • prevalence of premature neonates [ Time Frame: assessed at delivery date ]
    gestational age at delivery
  • number of a composite of adverse neonatal outcomes [ Time Frame: from delivery up neonates will be followed for the duration of the hospital stay, an expected average of 6 weeks ]
    Stillbirth, perinatal mortality, morbidity: chronic lung disease, neonatal sepsis, severe intra-ventricular haemorrhage (IVH) > grade II, periventricular leucomalacia > grade I, and necrotizing enterocolitis. Days on ventilation support, length of admission in neonatal intensive care, and total days in hospital until 3 months corrected age.
  • maternal well-being questionnaire, [ Time Frame: at baseline and each study visit/follow up measurement (at 1 week, 2 weeks, etc. up to 23 weeks after inclusion. The expected average is 8 weeks ]
    Reported medication side effects, and maternal well-being by signs and symptoms during pregnancy
  • number of assessed maternal complications [ Time Frame: from a study event participants will be followed for the duration of hospital stay, an expected average of 1 week ]
    Composite of maternal complications including: mortality, stroke, eclampsia, blindness, uncontrolled hypertension, respiratory failure, birth related variables, needed level of care
  • gestational age at the moment of progression to primary outcome. [ Time Frame: from baseline/inclusion until a study event is reached (up to 18 weeks after inclusion), with an expected average of 4 weeks. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 21, 2015)
  • the pattern of change of the hemodynamic profile, measured by the ratio of mean arterial pressure and heart rate. [ Time Frame: at baseline and each study visit/follow up measurement (at 1 week, 2 weeks, etc. up to 23 weeks after inclusion. The expected average is 8 weeks ]
    hemodynamic profiles will be classified as hyperdynamic, hypodynamic vasocontricted or mixed profile.
  • hemodynamic profile by mean arterial pressure/heart rate ratio [ Time Frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
    hemodynamic profiles will be classified as hyperdynamic, hypodynamic vasocontricted or mixed profile.
  • cardiac function measured by transthoracic echocardiography [ Time Frame: from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached) ]
    circulatory status, systolic and diastolic function
  • cardiac function measured by transthoracic echocardiography [ Time Frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
    circulatory status, systolic and diastolic function
  • cardiac remodeling during pregnancy: number of patients with concentric left ventricular remodeling or concentric hypertrophy. [ Time Frame: from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached) ]
    Echocardiographic concentric left ventricular (LV) remodelling and hypertrophy. Concentric remodeling is defined as a relative wall thickness (RWT) <=0.43 with a Left Ventricular Mass index (LVMi) of <95 gram/m2. Concentric hypertrophy is defined as a RWT <0.43 with a LVMi of ≥95 gram/m2.
  • cardiac remodeling during pregnancy: number of patients with concentric left ventricular remodeling or concentric hypertrophy. [ Time Frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
    Echocardiographic concentric left ventricular (LV) remodelling and hypertrophy. Concentric remodeling is defined as a relative wall thickness (RWT) <=0.43 with a Left Ventricular Mass index (LVMi) of <95 gram/m2. Concentric hypertrophy is defined as a RWT <0.43 with a LVMi of ≥95 gram/m2.
  • health status of the newborn by Apgar score [ Time Frame: assessed immediately after delivery ]
    scored by gynecologist or paediatrician on a scale of 1 to 10
  • prevalence of small for gestational age infancy and prevalence of premature neonates [ Time Frame: assessed at delivery date ]
    birth weight and percentile, gestational age at delivery
  • number of a composite of adverse neonatal outcomes [ Time Frame: from delivery up neonates will be followed for the duration of the hospital stay, an expected average of 6 weeks ]
    Stillbirth, perinatal mortality, morbidity: chronic lung disease, neonatal sepsis, severe intra-ventricular haemorrhage (IVH) > grade II, periventricular leucomalacia > grade I, and necrotizing enterocolitis. Days on ventilation support, length of admission in neonatal intensive care, and total days in hospital until 3 months corrected age.
  • maternal well-being questionnaire, [ Time Frame: at baseline and each study visit/follow up measurement (at 1 week, 2 weeks, etc. up to 23 weeks after inclusion. The expected average is 8 weeks ]
    Reported medication side effects, and maternal well-being by signs and symptoms during pregnancy
  • number of assessed maternal complications [ Time Frame: from a study event participants will be followed for the duration of hospital stay, an expected average of 1 week ]
    Composite of maternal complications including: mortality, stroke, eclampsia, blindness, uncontrolled hypertension, respiratory failure, birth related variables, needed level of care
  • gestational age at the moment of progression to primary outcome. [ Time Frame: from baseline/inclusion until a study event is reached (up to 18 weeks after inclusion), with an expected average of 4 weeks. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Early Vascular Adjustments During Hypertensive Pregnancy
Official Title  ICMJE Personalized Hemodynamically Guided Antihypertensive Treatment in Pregnant Women With Mild to Moderate Hypertension: a Randomized Controlled Trial
Brief Summary Paradoxical fetal and maternal results of studies have led to inconsistent use of antihypertensive drugs or no treatment at all in mild to moderate gestational hypertension in the Netherlands. However, none of the studies have taken the individual maternal circulatory state or the contemplated blood pressure response into account. Hypertension may be accompanied by high (hyperdynamic vasodilated profile), normal (normodynamic profile) of low (hypodynamic vasoconstrictive profile) cardiac output, and preeclampsia is not restricted to one circulatory profile. Therefore antihypertensive drugs should be viewed upon as correctors of the hemodynamic state rather than solely reducers of blood pressure. Without taking the maternal hemodynamic profile and condition into account, generic antihypertensive treatment can be expected to result in disappointing, inadequate and paradoxical results. The investigators hypothesize that in mild to moderate hypertension, personalized hemodynamically guided antihypertensive therapy (with target systolic and diastolic blood pressure <130/80mmHg), prevents the progression to severe hypertension and/or preeclampsia compared to no treatment, without the alleged side-effects.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Hypertension, Pregnancy-Induced
  • Pre-Eclampsia
Intervention  ICMJE
  • Drug: Labetalol
    Other Name: Trandate
  • Drug: Nifedipine
    Other Name: Adalat
  • Drug: Methyldopa
    Other Name: Aldomet
Study Arms  ICMJE
  • Active Comparator: randomized, interventiongroup
    Women with a hyperdynamic vasodilated profile, characterized by a mean arterial pressure (MAP)/ Heart rate (Hr) ratio ≤ 1.1 are prescribed a beta-blocker. Women with a hypodynamic vasoconstrictive profile (MAP/Hr ratio ≥ 1.4) are prescribed nifedipine. Women with normodynamic profile (MAP/Hr ratio in between 1.1 and 1.4) are prescribed Methyldopa.
    Interventions:
    • Drug: Labetalol
    • Drug: Nifedipine
    • Drug: Methyldopa
  • No Intervention: randomized, control-group
    Women who give informed consent for randomization, and are randomized to the control group will not be medicinally treated for mild to moderate gestational hypertension.
  • No Intervention: not-randomized, control-group
    Women who do not want to be randomized, but who give informed consent for follow-up on their data until discharge after delivery. They will receive standard care, i.e. no medication is prescribed for mild to moderate gestational hypertension.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 21, 2015)
368
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2021
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients ages 18years or older
  • Before 37 weeks of gestational age;
  • Diagnosed with mild to moderate gestational hypertension

Exclusion Criteria:

  • Women with severe hypertension: systolic blood pressure ≥ 160mmHg and/or diastolic blood pressure ≥ 110mmHg.
  • Women with chronic hypertension who are already on antihypertensive drugs. If no antihypertensive drugs are used yet, women with pre-existent hypertension are eligible to participate.
  • Women diagnosed with preeclampsia or eclampsia in the current pregnancy.
  • Women who are not able to comprehend the study outline.
  • Women who have already participated in this study cannot be included a second time.
  • Women who have a (relative) contra-indication for one of the possible prescribed medications (for example women who have tested positive for antinuclear antibodies, which is a contraindication for Methyldopa).
  • Women who intend to terminate the pregnancy
  • Women who have a fetus with a major anomaly or chromosomal abnormality
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Eva Mulder, MD 0031650504243 eva.mulder@mumc.nl
Contact: Marc Spaanderman, professor 0031433874774 marc.spaanderman@mumc.nl
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02531490
Other Study ID Numbers  ICMJE METC152017
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Maastricht University Medical Center
Study Sponsor  ICMJE Maastricht University Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Marc Spaanderman, professor Maastricht University Medical Centre
PRS Account Maastricht University Medical Center
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP